Cost-effective strategies for CAR-T cell therapy manufacturing

Abstract

CAR-T cell therapy has revolutionized cancer treatment, with approvals for conditions like acute B-leukemia, large B cell lymphoma (LBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and multiple myeloma. However, its high costs limit accessibility. Key factors driving these costs include the need for personalized, autologous treatments, transportation to specialized facilities, reliance on viral vectors requiring advanced laboratories, and lengthy cell expansion processes. To address these challenges, alternative strategies aim to simplify and reduce production complexity. Non-viral vectors, such as Sleeping Beauty, piggyBac, and CRISPR, delivered via nanoparticles or electroporation, present promising solutions. These methods could streamline manufacturing, eliminate the need for viral vectors, and reduce associated costs. Furthermore, shortening cell expansion periods and optimizing protocols could significantly accelerate production. An emerging approach involves using genetically edited T cells from healthy donors to create universal CAR-T products capable of treating multiple patients. Finally, decentralized point-of-care (POC) manufacturing of CAR-T cells minimize logistical expenses, eliminating the need for complex infrastructure, and enabling localized production closer to patients. This innovative strategy holds potential for broadening access and reducing costs, representing a step toward democratizing CAR-T therapy. Combined, these advances could make this groundbreaking treatment more feasible for healthcare systems worldwide.

Keywords: B cell tumor; CAR-T cell; MT: Regular Issue; cost-effective; immunotherapy; manufacturing.

Graphical abstract

Figure 1

CAR-T cell product manufacturing involves several steps, which increase the complexity and cost of this therapy After a patient is indicated for this therapy, the procedure is generally divided into two main phases: the steps carried out in the hospital (shown in purple) and the steps carried out in the manufacturing unit (shown in blue). In the hospital, the patient undergoes leukapheresis and cryopreservation of the cells (if required). The cells are then transported to the production center, which may be in a different country. At the manufacturing unit, T cells are isolated, activated, modified to express the CAR through viral transduction, expanded for several days, frozen, and subjected to quality control. The cells are then shipped back to the hospital. Finally, the patient undergoes conditioning and receives the CAR-T cells. This procedure can take up to one month, depending on the origin of the cells. Efforts to simplify and optimize this production process are currently underway, with major points for improvement highlighted in red in the figure.

Figure 2

Reduced expansion time of CAR-T cells contributes to the optimization of the production protocol for these cells The automation of the CAR-T cell production process using a closed system can help reduce the production time of the cell product and eliminate the need for transportation to specialized centers. This approach essentially involves removing cells from the patient, modifying them using non-viral methods (such as transposons, nanoparticles, or CRISPR), performing quality control, and reinfusing them into the patient. This process can be completed in just one day.

Figure 3

Off-the-shelf CAR-T cells offer an alternative to reduce both the time and cost for patients to receive treatment Currently, most CAR-T cell therapies are autologous, involving the extraction, modification, and reinfusion of a patient’s own cells—a process that can take up to three weeks. An alternative to streamline this process is to utilize universal CAR-T cells derived from allogeneic donors, producing multiple doses to treat several patients in less than a week. This approach is referred to as off-the-shelf CAR-T cell therapy. In addition to reducing time and cost, donor cells may be healthier, as they have not been exposed to the invasive treatments that cancer patients typically undergo, such as chemotherapy and radiotherapy.